Discover. Oncology最新文献

{"title":"Immune-oncology targets and therapeutic response of cell pyroptosis-related genes with prognostic implications in neuroblastoma.","authors":"Xingyu Liu, Zhongya Xu, Hanjun Yin, Xu Zhao, Jinjiang Duan, Kai Zhou, Qiyang Shen","doi":"10.1007/s12672-024-01518-8","DOIUrl":"10.1007/s12672-024-01518-8","url":null,"abstract":"<p><strong>Objective: </strong>Construction of a neuroblastoma (NB) prognostic predictive model based on pyroptosis-related genes (PRGs) to improve individualized management of NB patients.</p><p><strong>Methods: </strong>The NB cohort GSE49711 was obtained from the Gene Expression Omnibus (GEO) database, and a total of 498 patients were enrolled into the study, which were randomized into a training set and a test set at a ratio of 1:1, with 250 patients in the training set and 248 patients in the test set. A risk prediction model was constructed using the training set, and the GSE49711 cohort and test set were used as internal validation to verify the reliability of the model. Independent predictors associated with prognosis were screened using univariate and multivariate COX regression analyses, and risk score models were constructed. Single-cell gene set enrichment analysis (ssGSEA) was used to assess the relationship between PRGs and the tumor immune microenvironment. Nomograms were constructed to extend the clinical usability of the model and the reliability of the model was verified using ROC curves and calibration curves. Protein interaction networks of risk genes were mapped using the String database, and the expression of PRGs in NB cell lines was staged using the CCLE database.</p><p><strong>Results: </strong>A prognostic model was first developed with the training set: the risk score formula was (- 0.30 × GSDMB) + (- 0.46 × IL-18) + (- 0.21 × NLRP3) + (0.56 × AIM2). Patients were categorized into high- and low-risk groups based on the median risk score value. Survival analysis showed that NB patients in the high-risk group had a significantly lower survival rate than those in the low-risk group (P < 0.001). In both the GSE49711 overall cohort and the test cohort, survival analyses showed that patients in the high-risk group had significantly lower survival than those in the low-risk group (P < 0.001). Single-cell gene set enrichment analysis was used to assess the relationship between PRGs and the tumor immune microenvironment. Time-dependent ROC curves assessed the predictive performance of the nomogram in 5-, 7.5-, and 10-year survival with areas under the curve (AUC) of 0.843, 0.802 and 0.797, respectively. The calibration curves show good clinical predictive performance for nomograms.</p><p><strong>Conclusion: </strong>The results suggest that PRGs may serve as a novel prognostic marker for NB patients to provide new immunotherapeutic targets for the clinical treatment of NB patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Succinylation modification-mediated upregulation of Sp1 promotes hepatocellular carcinoma cell proliferation.","authors":"Yehong Han, Xueqin Deng, Haixia Chen, Jie Chen, Wei Xu, Lanqin Liu","doi":"10.1007/s12672-024-01533-9","DOIUrl":"10.1007/s12672-024-01533-9","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains one of the most prevalent malignant tumors globally, characterized by high incidence and mortality rates. Despite ongoing research, the underlying molecular mechanisms of HCC development are not yet fully understood. Utilizing bioinformatic analysis, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot assays, we identified that the expression of specificity protein 1 (Sp1) was significantly elevated in HCC cells compared to normal cells. Knockdown of the Sp1 gene led to a marked reduction in the viability and clonogenic potential of HCC cells. Further investigation revealed that the succinylation level of Sp1 was also increased in HCC cells. The upregulation of Sp1 expression was attributed to its succinylation, mediated by KAT2A, with lysine (K)562 identified as the succinylation site. Additionally, KAT2A and Sp1 were found to influence the upregulation of mTOR phosphorylation. Collectively, these findings suggest that KAT2A-promoted succinylation of Sp1 enhances the proliferative capacity of HCC cells by activating the mTOR pathway, providing a theoretical foundation for potential therapeutic strategies against HCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology and in vitro experiments to investigate the anti-gastric cancer effects of paeoniflorin through the RAS/MAPK signaling pathway.","authors":"Yating Yang, Ling Yuan, Yuhua Du, Mengyi Ye, Doudou Lu, Shicong Huang, Jianjun Zhao, Joanna Japhet Tibenda, Fandi Meng, Yi Nan","doi":"10.1007/s12672-024-01532-w","DOIUrl":"10.1007/s12672-024-01532-w","url":null,"abstract":"<p><p>The aim of this study was to investigate the key targets and signaling pathways of paeoniflorin (PF) for the treatment of gastric cancer (GC). First, the differentially expressed genes (DEGs) of gastric cancer were obtained by analyzing GSE118916 Gene Chip, and then the active components of paeoniflorin and their targets of action were found. And the intersection genes of the two were analyzed for target and pathway analysis. In addition, cell viability after PF intervention was detected by CCK-8. Clone formation assay, wound scratch assay, transwell assay were used to detect cell migration and invasion. The qRT-PCR and Western blot methods were used to verify the mechanism of action. The results showed that a total of 286 paeoniflorin targets and 1799 DEGs were obtained. Secondly, we found that PF could treat gastric cancer through RAS/MAPK signaling pathway. In addition, through in vitro cellular experiments, we also found that PF had a significant therapeutic effect on gastric cancer. Therefore, we believe that PF inhibits the proliferation and metastasis of gastric cancer, and its effect may be exerted by regulating the RAS/MAPK signaling pathway. PF is a promising drug for the treatment of gastric cancer. Combined with the in vitro experiments, we found that the therapeutic effect of PF is related to the regulation of the RAS/MAPK signaling pathway, and the results of the present study preliminarily revealed its complex mechanism, which will lay the foundation for future clinical treatment.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of kaempferol in digestive system tumors: recent advances and mechanistic insights.","authors":"Xunxing Hao, Meng Ding, Chenyu Chi, Xiaodong Xu, Xiaoyu Zhang, Mingzhe Hu","doi":"10.1007/s12672-024-01510-2","DOIUrl":"10.1007/s12672-024-01510-2","url":null,"abstract":"<p><p>Digestive system neoplasms are a heterogeneous group of cancers characterized by diverse symptoms, complex diagnosis, and treatment. Prognosis is poor and influenced by multiple factors, making early detection and comprehensive treatment crucial for patient survival. Kaempferol, a flavonoid compound, has attracted attention due to its anti-tumor biological activity, holding promise as a potential drug for treating digestive system neoplasms. Derived from various plants such as cabbage, propolis, and grapefruit, this compound's anti-inflammatory, antioxidant, and other pharmacological effects have been confirmed. Research has found that kaempferol inhibits the occurrence and development of digestive system neoplasms by inducing apoptosis in cancer cells, inhibiting tumor cell proliferation, suppressing tumor metastasis and invasion, and enhancing the effects of other cancer treatment methods. This paper summarizes the role and mechanisms of kaempferol in the study of digestive system neoplasms, providing valuable insights for both scientists and clinical physicians engaged in this field. By detailing the various pathways through which kaempferol exerts its anticancer effects, the paper not only highlights its potential as a therapeutic agent but also opens avenues for further research into its applications.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiotherapy in patients with brain metastases with and without concomitant immunotherapy: comparison of patient outcome and neurotoxicity.","authors":"Natalie Elyan, Philipp Schwenkenbecher, Lea Grote-Levi, Jan-Niklas Becker, Roland Merten, Hans Christiansen, Thomas Skripuletz, Diana Steinmann, Nora Möhn","doi":"10.1007/s12672-024-01560-6","DOIUrl":"10.1007/s12672-024-01560-6","url":null,"abstract":"<p><strong>Background/aim: </strong>Recently, immune checkpoint inhibitors (ICI) have been added to the treatment of brain metastases. While combining radiotherapy and ICI can enhance therapeutic effects, it might also increase the risk of severe autoimmune adverse events. This retrospective study aims to compare treatment responses and neurotoxicity in patients treated with radiotherapy alone versus those receiving a combination of radiotherapy and ICI.</p><p><strong>Patients and methods: </strong>All patients with brain metastases who received radiotherapy at Hannover Medical School from 2017 to 2019 were included. The medical reports of all study participants were evaluated. Patients who received radiotherapy alone and those who received a combination of radiation and ICI were compared.</p><p><strong>Results: </strong>A total of 248 patients were analyzed, with the most common tumor types being non-small cell lung cancer (NSCLC) and malignant melanoma. Half of the patients received whole-brain radiotherapy (WBRT) and the other half stereotactic radiotherapy (SRT). Of these, 29 patients received concurrent immunotherapy and radiotherapy, 30 completed immunotherapy before radiotherapy, and 29 started ICI after completing radiotherapy. Two cases lacked information on the duration of immunotherapy. Overall survival post-initial tumor diagnosis within the total cohort was 52 months, with significantly worse survival for patients with multiple brain metastases (p = 0.020). No significant differences in survival or incidence of neurological adverse events were observed between patients with or without ICI.</p><p><strong>Conclusion: </strong>Combining radiotherapy and ICI did not significantly increase neurotoxicity or improve survival in this cohort, though the heterogeneity of the subgroups limits the generalizability of these findings.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival prediction in patients with head and neck squamous cell carcinoma and novel mechanistic insights of S100A8/A9.","authors":"Yihong Hu, Minhui He, Yucheng Han, Lu Zeng, Ziwei Ma, Xianqiong Zou","doi":"10.1007/s12672-024-01540-w","DOIUrl":"10.1007/s12672-024-01540-w","url":null,"abstract":"<p><strong>Background: </strong>S100A8/A9, an innate immune protein, significantly regulates inflammatory processes and immune responses. While S100A8/A9 has been linked to various diseases, its association with head and neck squamous cell carcinoma (HNSCC) remains unclear.</p><p><strong>Methods: </strong>Samples from the Cancer Genome Atlas (TCGA) were categorized into groups with low and high expression of S100A8/A9. R software, Sangerbox, UALCAN, GEPIA2, STRING, Cytoscape, TCGC Data Portal, miRcode, OncomiR and ENCORI databases were used to comprehensively study the expression, interactome and mutational profiles of S100A8/A9 and associated mechanism in HNSCC.</p><p><strong>Results: </strong>The proteins S100A8/A9 were found to be associated with processes of 'epithelium development', 'regulating pluripotency of stem cells' and 'regulation of immune system'. The most frequent mutation observed in the S100A8 protein was E93K (3/37, MU4401889), while for the S100A9 protein, it was R10C (4/37, MU4633862). Furthermore, the group expressing high levels of S100A8/A9 showed increased infiltration by dendritic cells and neutrophils, but decreased infiltration by M2 macrophages, compared to the group with low S100A8/A9 expression. S100A8/A9 was also found to interact with a variety of mRNA transcripts, several of which were involved in initiation and progression of HNSCC. Through LASSO-Cox method, 20 genes (CALML5, MSX1, FZD3, STC2, SLC2A3, TMEM198B, DYNC1I1, SPHK2, ALMS1.IT1, SPPL2B, PDGFA, BCORL1, TEX101, SGCE, DNAJC12, RRN3P1, HOXB9, TMEM150C, METTL7B and PSPN) were screening to construct a prognostic model to distinguish favorable and poor prognosis of HNSCC patients. Besides, our prognostic model was also validated in GSE41613 cohort.</p><p><strong>Conclusions: </strong>S100A8/A9 may be a promising marker for the diagnostic and prognostic assessment of the HNSCC patients. Based on these insights, we have devised a new classification model for HNSCC, which has the potential to enhance the management and personalized treatment of HNSCC patients. The model should also be further optimized through the expansion of sample size and implemented experimental studies in future research.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between glucose metabolism and body mass index in tumor lesions of patients with lung cancer.","authors":"Zhengqin Zhao, Xiaona Wang, Dong Wang, Jiahui Zhang, Hongjie Yang","doi":"10.1007/s12672-024-01539-3","DOIUrl":"10.1007/s12672-024-01539-3","url":null,"abstract":"<p><strong>Objective: </strong>Lung cancer, along with various other cancers, is characterized by increased glucose metabolism. The maximum standardized uptake value (SUVmax), derived from positron emission tomography-computed tomography (PET-CT), serves as an indicator of glucose metabolic activity in tumor lesions. This study aimed to evaluate the correlation between body mass index (BMI) and SUVmax in individuals with lung cancer.</p><p><strong>Methods: </strong>This study included 41 patients with lung cancer, who were divided into two groups: Group 1 (n = 21), with a BMI greater than 22.4, and Group 2 (n = 20), with a BMI less than 22.4. All participants underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging. The SUVmax was calculated by manually delineating the regions of interest. A t-test was performed to assess whether the differences in SUVmax between the two groups were statistically significant.</p><p><strong>Results: </strong>The mean SUVmax for Group 1 was 11.20 ± 5.45, while for Group 2 it was 10.65 ± 5.96. Although the mean SUVmax was higher in Group 1 compared to Group 2, the difference between the groups was not statistically significant (P = 0.757).</p><p><strong>Conclusion: </strong>The findings indicate a non-significant difference in glucose metabolism in lung cancer lesions between patients with different BMI levels. These results offer valuable insights into the metabolic characteristics of lung cancer and contribute to a deeper understanding of its pathophysiology.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis of STAT3 indicates its potential prognostic value and correlation with immune cell infiltration in prostate cancer.","authors":"Zhouting Tuo, Hesong Zhang, Ke He, Zhiwei Jiang, Chao Jiang, Xin Chen, Haichao Yuan","doi":"10.1007/s12672-024-01527-7","DOIUrl":"10.1007/s12672-024-01527-7","url":null,"abstract":"<p><strong>Background: </strong>Targeting the STAT3 signaling pathway is a promising therapeutic approach for cancer patients. However, the association between STAT3 expression, the tumor immune microenvironment, and genetic variation remains unclear across human cancers, especially prostate cancer.</p><p><strong>Methods: </strong>We used R software and other tools to analyze pan-cancer and mutation data from publicly available databases statistically. A comprehensive investigation was performed to assess the genetic heterogeneity and clinical relevance of STAT3 in various malignancies, with a specific focus on its role in the immune landscape and prognostic significance in prostate cancer. The findings were validated through immunohistochemistry (IHC) and multiplex immunofluorescence (mIF).</p><p><strong>Results: </strong>STAT3 expression is abnormal in the majority of cancer tissues, which is strongly correlated with these patients' prognosis. Eight measures of tumor heterogeneity and six measures of tumor stemness of multiple tumor types showed a strong correlation with STAT3 expression. Furthermore, in individuals with prostate cancer, STAT3 expression indicated the degree of immune cell infiltration and the advancement of the disease. IHC analysis revealed that STAT3 was down-regulated in prostate tumor tissues, while mIF analysis demonstrated that STAT3 signaling (p-STAT3) was extensively active in tumor tissues and positive lymph node tissues.</p><p><strong>Conclusion: </strong>STAT3 may serve as a valuable prognostic biomarker and therapeutic target across various cancers, with particular relevance to prostate cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding serine and glycine metabolism in cancer: a path towards precision medicine to improve patient's outcomes.","authors":"Anaís Sánchez-Castillo, Kim R Kampen","doi":"10.1007/s12672-024-01544-6","DOIUrl":"10.1007/s12672-024-01544-6","url":null,"abstract":"<p><p>In this perspective, we highlight and reflect on the current knowledge with respect to serine/glycine metabolism in cancer, therapeutic resistance, and precision medicine opportunities for therapeutic targeting and treatment follow-up. Cancer subtypes with high mortality rates include lung cancer and glioblastomas. In order to improve future therapeutic opportunities, patient stratification need to be performed to select patients that might benefit from adjuvant serine/glycine targeting compounds. In an effort to identify the group of patients for stratification purposes, we analyzed publicly available TCGA patient datasets to test associations between serine/glycine metabolism enzyme expression and important cancer drivers in lung cancer and glioblastoma. These patients presenting serine/glycine pathway overexpression might benefit from adjuvant sertraline treatment in the future.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing hypoxia and lactate metabolism-related molecular subtypes and prognostic signature for clear cell renal cell carcinoma through integrating machine learning.","authors":"Jinhui Liu, Tianliu Yang, Jiayuan Liu, Xianghui Hao, Yuhang Guo, Sheng Luo, Benzheng Zhou","doi":"10.1007/s12672-024-01543-7","DOIUrl":"10.1007/s12672-024-01543-7","url":null,"abstract":"<p><strong>Background: </strong>The microenvironment of clear cell renal cell carcinoma (ccRCC) is characterized by hypoxia and increased lactate production. However, the impact of hypoxia and lactate metabolism on ccRCC remains incompletely understood. In this study, a new molecular subtype is developed based on hypoxia-related genes (HRGs) and lactate metabolism-related genes (LMRGs), aiming to create a tool that can predict the survival rate, immune microenvironment status, and responsiveness to treatment of ccRCC patients.</p><p><strong>Method: </strong>We obtained RNA-seq data and clinical information of patients with ccRCC from TCGA and GEO. HRGs and LMRGs are sourced from the Molecular Signatures Database. Integrating 10 machine learning algorithms and 101 frameworks, we constructed a prognostic model related to hypoxia and lactate metabolism. Its accuracy and reliability are evaluated through constructing prognostic nomograms, drawing ROC curves, and validating with clinical datasets. Additionally, risk subgroups are evaluated based on functional enrichment, tumor mutational burden (TMB), immune cell infiltration degree, and immune checkpoint expression level. Finally, we evaluate the responsiveness of risk subgroups to immunotherapy and determine personalized drugs for specific risk subgroups.</p><p><strong>Results: </strong>85 valuable prognostic genes were screened out. Functional enrichment analysis shows that the group with high-risk hypoxia and lactate metabolism-related genes scores (HLMRGS) is mainly involved in the activation of immune-related activities, while the low risk HLMRGS group is more active in metabolic and tumor-related pathways. At the same time, differences in the cellular functional states in the tumor microenvironment between the high risk HLMRGS group and the low risk HLMRGS group were observed. Finally, potential drugs for specific risk subgroups were determined.</p><p><strong>Conclusion: </strong>We have developed a novel prognostic signature that integrates hypoxia and lactate metabolism. It is expected to become an effective tool for prognosis prediction, immunotherapy and personalized medicine of ccRCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}